Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells

J Clin Invest. 1998 Aug 1;102(3):576-83. doi: 10.1172/JCI181.


Formation of the atherosclerotic intima must involve altered metabolism of the elastin-rich arterial extracellular matrix. Proteases potentially involved in these processes remain unclear. This study examined the expression of the potent elastases cathepsins S and K in human atheroma. Normal arteries contained little or no cathepsin K or S. In contrast, macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Intimal smooth muscle cells (SMC), especially cells appearing to traverse the internal elastic laminae, also contained these enzymes. Extracts of atheromatous tissues had approximately twofold greater elastase-specific activity than extracts of uninvolved arteries, mostly due to cysteine proteases. Cultured human SMC displayed no immunoreactive cathepsins K and S and exhibited little or no elastolytic activity when incubated with insoluble elastin. SMC stimulated with the atheroma-associated cytokines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (15-20 microg/10(6) cells/24 h). A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity. The presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for elastolytic cathepsins in vessel wall remodeling and identifies novel therapeutic targets in regulating plaque stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arteriosclerosis / enzymology*
  • Arteriosclerosis / genetics
  • Carotid Stenosis / enzymology
  • Carotid Stenosis / genetics
  • Cathepsin K
  • Cathepsins / biosynthesis*
  • Cathepsins / genetics
  • Cells, Cultured
  • Coronary Disease / enzymology
  • Coronary Disease / genetics
  • Elastin / metabolism*
  • Enzyme Induction
  • Humans
  • Interferon-gamma / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Tunica Intima / cytology
  • Tunica Intima / metabolism


  • RNA, Messenger
  • Interferon-gamma
  • Elastin
  • Cathepsins
  • cathepsin S
  • CTSK protein, human
  • Cathepsin K